1. Field of the Invention
The invention relates to a pharmaceutical and a method for treating patients with high blood pressure and, more particularly, to the use of reduced forms of nicotinamide adenine dinucleotide (NADH), nicotinamide adenine dinucleotide phosphate (NADPH), and physiologically acceptable salts thereof in the treatment of hypertension.
2. Description of Related Art
Hypertension, a major public health problem, is defined as the condition of having blood pressure (BP) exceeding an upper limit of normality. The upper limit is generally accepted as a systolic BP&gt;140 mg Hg and/or diastolic BP&gt;90 mg Hg. This perturbation is a major risk factor for cardiovascular diseases (CVD) which account for approximately 50% of mortality beyond age 65.
It is generally accepted that a significant elevation of blood pressure can accelerate the aging process in the circulatory system. During aging, many factors involved in regulating blood pressure can go awry. Therefore it is not surprising that systolic and diastolic blood pressure increase progressively with aging, a phenomenon which is called "age-related hypertension." Hypertension is found in 50% or more of individuals above age 55 years, and 63% of those age 65 to 74 years. The rate is 76% among persons of African origin over 65 years old in the United States. This age-related hypertension, particularly of the diastolic blood pressure, is most likely due to the reduced elasticity of the blood vessels or, even worse, stiffness of the blood vessels. This reduced elasticity may be caused by damage of the muscle layer of the blood vessels. This damage can be caused by radicals from chemicals, radiation or other toxins. Due to this, these endothelial muscles cannot function properly contracting and relaxing when blood pressure demand makes that necessary. The consequence is a higher diastolic blood pressure.
There are numerous substances in use against higher blood pressure such as angiotensin-converting enzyme (ACE) inhibitors, anti-sympaticotonica, beta-blockers, calcium-antagonists, diuretics, vasodilatators and all kinds of combinations. However, all these drugs are synthetic chemical substances which do not occur naturally in the human body. It would be very desirable to discover an endogenous substance which can regulate high blood pressure.
Nicotinamide-adenine-dinucleotide in its reduced form ("NADH") and nicotinamide-adenine-phosphate-dinucleotide in its reduced form ("NADPH") are physiological substances which occur in all living cells including human cells. These substances are cofactors for a variety of enzymes, the majority of which catalyze oxidation-reduction reactions. Prior to recent discoveries as to certain therapeutic properties of these compounds, their principal utility has been as diagnostic tools in clinical biochemistry and as essential components in reaction kits, for example, in measuring lactatdehydrogenase (LDH).
The most important function of NADH is its driving force for cell respiration. When using oxygen, NADH forms water and 3 ATP molecules in accordance with the following formula: NADH+H.sup.+ +1/2 O.sub.2 +3 Pi+3 ATP.fwdarw.NAD.sup.+ +3 ATP+4H.sub.2 O. Thus, with 1 NADH molecule, 3 ATP molecules are obtained which have an energy of approximately 21 kilocalories. This process is called oxidative phosphorylation. The supply of NADH and/or NADPH makes this work much easier for the organism, because it has greater energy reserves as a result.
More recently, NADH and NADPH and pharmaceutically acceptable salts thereof have been shown to be useful in the treatment of Parkinson's Disease. The effectiveness of these agents for this purpose is documented in my U.S. Pat. Nos. 4,970,200 and 5,019,561, the disclosures of which are incorporated herein by reference.
In addition, I have discovered that these substances are effective in the treatment of Morbus Alzheimer (i.e., Alzheimer's Disease), which is the subject of my U.S. Pat. No. 5,444,053.
Prior to my recent discoveries, NADH and NADPH have never been considered for therapeutic use, probably because it was believed that these compounds are rather unstable and, hence, not capable of being absorbed by the intestines of the human body. It would have been expected that these substances would be hydrolized in the plasma within a few seconds.
However, studies performed recently using NADH and NADPH demonstrate that these assumptions are incorrect. When NADH and NADPH were applied intravenously to patients with Parkinson's disease, a remarkable beneficial effect was observed which lasted at least 24 hours. See U.S. Pat. Nos. 4,970,200 and 5,019,561. This indicates that NADH and NADPH are not rapidly degraded in the plasma and blood.